Abstract

MOPE237 - Poster Exhibition

Safety and efficacy of maraviroc (MVC) in CCR5-tropic HIV-1-infected children aged 2 to < 18 years

C. Giaquinto¹, J. Fourie², I. Mitha³, A. Fang⁴, M. Vourvahis⁵, L. McFadyen⁶, S.R. Valluri⁴, C. Craig⁶, G. Mukwaya⁴, H. Valdez⁴, J. Heera<sup>5

1</sup>University of Padova, Pediatrics Department, Padova, Italy, ²Dr. J Fourie Medical Centre, Dundee, South Africa, ³Benmed Clinic, Benoni, Gauteng, South Africa, ⁴Pfizer, Inc., New York, United States, ⁵Pfizer, Inc., New London, United States, ⁶Pfizer, Sandwich, United Kingdom

Background: Maraviroc (MVC) is a CCR5 antagonist, approved to treat adults infected with CCR5-tropic HIV-1 but not yet approved for pediatric use.
Methods: This is an open-label, two-stage (stage 1: dose-finding; stage 2: safety/efficacy evaluation), age-stratified, non-comparative, multi-center study to evaluate safety, tolerability, and pharmacokinetics of MVC plus optimized background therapy (OBT) in treatment-experienced children. Subjects infected with CCR5-tropic HIV-1 are enrolled into one of four age/formulation cohorts (table).
Results: Thirty-one subjects were enrolled by 08/27/2010, initially dosed according to body surface area and OBT interactions with MVC. Dose adjustment occurred if average concentrations < 100 ng/mL at Week 2. Maintenance MVC doses ranged from 50-450 mg BID.

Subject Characteristics	Cohort 1: ³2 - <6 years Liquid MVC (N=2)	Cohort 2: ³6 - <12 years Tablet MVC (N=12)	Cohort 3: ³6 - <12 years Liquid MVC (N=5)	Cohort 4: ³12 - <18 years Tablet MVC (N=12)
Sex (Males/Females)	2 / 0	5 / 7	3 / 2	4 / 8
Race (White/Black/Asian)	0 / 0 / 2	3 / 8 / 1	1 / 4 / 0	4 / 6 / 2
Median treatment duration (days)	200	341	322	166
Median baseline log10 RNA (copies/mL)	5.7	4.3	4.9	4.7
Median baseline CD4+ counts (µ/L)	151	478	192	312

[Table 1]


Five subjects had six treatment-emergent, non-treatment-related serious adverse events (AEs): uncontrolled behavior, prurigo, pneumonia, gastrocutaneous fistula, H1N1 infection, and pulmonary tuberculosis. Five subjects experienced 11 treatment-related AEs (all ≤Grade-2): vomiting, elevated liver enzymes, nightmares, cardiac murmur, prurigo, abdominal pain, skin rash, decreased appetite, dizziness (2), and depression. Eight subjects had nine Grade-3 abnormal laboratory results: hyponatremia (4), neutropenia (4), and hypercholesterolemia (1). No deaths or discontinuations due to AEs occurred. HIV RNA < 48 copies/mL was achieved in 13/20 (65%) and 6/9 (67%) patients at Weeks 24 and 48, respectively. Eight subjects discontinued; four with virologic failure without tropism change or MVC resistance at failure time, but with pharmacokinetic evidence of poor adherence.
Conclusion: Preliminary data suggest that MVC plus OBT in treatment-experienced children was safe, well tolerated, and effective. Enrollment is continuing.
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